CA2653101A1 - Preparations et methodes pour la liberation d'oxyde nitrique - Google Patents
Preparations et methodes pour la liberation d'oxyde nitrique Download PDFInfo
- Publication number
- CA2653101A1 CA2653101A1 CA002653101A CA2653101A CA2653101A1 CA 2653101 A1 CA2653101 A1 CA 2653101A1 CA 002653101 A CA002653101 A CA 002653101A CA 2653101 A CA2653101 A CA 2653101A CA 2653101 A1 CA2653101 A1 CA 2653101A1
- Authority
- CA
- Canada
- Prior art keywords
- nox
- protein
- wild
- type
- tengcongensis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 152
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title description 951
- 239000000203 mixture Substances 0.000 title description 32
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 1172
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 1167
- 230000035772 mutation Effects 0.000 claims abstract description 189
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 115
- 210000004369 blood Anatomy 0.000 claims abstract description 18
- 239000008280 blood Substances 0.000 claims abstract description 18
- 241000253373 Caldanaerobacter subterraneus subsp. tengcongensis Species 0.000 claims description 381
- 241000700157 Rattus norvegicus Species 0.000 claims description 281
- 241000282414 Homo sapiens Species 0.000 claims description 226
- 238000010494 dissociation reaction Methods 0.000 claims description 189
- 230000005593 dissociations Effects 0.000 claims description 189
- 108010054147 Hemoglobins Proteins 0.000 claims description 119
- 102000001554 Hemoglobins Human genes 0.000 claims description 119
- 230000009257 reactivity Effects 0.000 claims description 114
- 150000003278 haem Chemical class 0.000 claims description 110
- 241000255601 Drosophila melanogaster Species 0.000 claims description 78
- 238000006701 autoxidation reaction Methods 0.000 claims description 78
- 150000001413 amino acids Chemical class 0.000 claims description 75
- 108020004707 nucleic acids Proteins 0.000 claims description 57
- 102000039446 nucleic acids Human genes 0.000 claims description 57
- 241000193401 Clostridium acetobutylicum Species 0.000 claims description 48
- 150000007523 nucleic acids Chemical class 0.000 claims description 47
- 101100121602 Caenorhabditis elegans gcy-35 gene Proteins 0.000 claims description 41
- 241000256182 Anopheles gambiae Species 0.000 claims description 34
- 241000699660 Mus musculus Species 0.000 claims description 34
- 241000605739 Desulfovibrio desulfuricans Species 0.000 claims description 32
- 206010020772 Hypertension Diseases 0.000 claims description 31
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 30
- 241000010804 Caulobacter vibrioides Species 0.000 claims description 26
- 241001223867 Shewanella oneidensis Species 0.000 claims description 26
- 241000424623 Nostoc punctiforme Species 0.000 claims description 24
- 108090000144 Human Proteins Proteins 0.000 claims description 23
- 102000003839 Human Proteins Human genes 0.000 claims description 23
- 241000193155 Clostridium botulinum Species 0.000 claims description 21
- 241000283690 Bos taurus Species 0.000 claims description 19
- 102000008300 Mutant Proteins Human genes 0.000 claims description 19
- 108010021466 Mutant Proteins Proteins 0.000 claims description 19
- 102220469353 Putative uncharacterized protein URB1-AS1_N74A_mutation Human genes 0.000 claims description 19
- 102220040905 rs150548839 Human genes 0.000 claims description 19
- 241000276569 Oryzias latipes Species 0.000 claims description 18
- 102220225960 rs199780731 Human genes 0.000 claims description 17
- 102220597048 Essential MCU regulator, mitochondrial_Y40V_mutation Human genes 0.000 claims description 16
- 241000255908 Manduca sexta Species 0.000 claims description 16
- 108010077805 Bacterial Proteins Proteins 0.000 claims description 15
- 102220595179 Casein kinase II subunit alpha'-interacting protein_F78W_mutation Human genes 0.000 claims description 15
- 101100504294 Drosophila melanogaster Gyc88E gene Proteins 0.000 claims description 14
- 241001441722 Takifugu rubripes Species 0.000 claims description 14
- 241000607626 Vibrio cholerae Species 0.000 claims description 14
- 101100121600 Caenorhabditis elegans gcy-33 gene Proteins 0.000 claims description 13
- 101100121603 Caenorhabditis elegans gcy-36 gene Proteins 0.000 claims description 13
- 241000282472 Canis lupus familiaris Species 0.000 claims description 13
- 241000269368 Xenopus laevis Species 0.000 claims description 13
- 239000002202 Polyethylene glycol Substances 0.000 claims description 12
- 210000004027 cell Anatomy 0.000 claims description 12
- 229920001223 polyethylene glycol Polymers 0.000 claims description 12
- 101100121598 Caenorhabditis elegans gcy-31 gene Proteins 0.000 claims description 11
- 101100121599 Caenorhabditis elegans gcy-32 gene Proteins 0.000 claims description 11
- 206010019280 Heart failures Diseases 0.000 claims description 11
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 11
- 230000007812 deficiency Effects 0.000 claims description 11
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 11
- 201000006370 kidney failure Diseases 0.000 claims description 11
- 101100121601 Caenorhabditis elegans gcy-34 gene Proteins 0.000 claims description 10
- 101100121604 Caenorhabditis elegans gcy-37 gene Proteins 0.000 claims description 10
- 239000002502 liposome Substances 0.000 claims description 10
- 239000002105 nanoparticle Substances 0.000 claims description 10
- 230000003639 vasoconstrictive effect Effects 0.000 claims description 10
- 239000013598 vector Substances 0.000 claims description 10
- 241001599018 Melanogaster Species 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 102220036164 rs587777304 Human genes 0.000 claims description 4
- 230000032258 transport Effects 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 2
- 241000078742 Viola fischerii Species 0.000 claims 6
- 102200132744 rs137853222 Human genes 0.000 claims 2
- 206010008631 Cholera Diseases 0.000 claims 1
- 102220573186 Protein adenylyltransferase SelO, mitochondrial_F79Y_mutation Human genes 0.000 claims 1
- 230000027455 binding Effects 0.000 abstract description 71
- 239000000969 carrier Substances 0.000 abstract description 29
- 239000003446 ligand Substances 0.000 abstract description 22
- 238000011282 treatment Methods 0.000 abstract description 11
- 230000009286 beneficial effect Effects 0.000 abstract description 8
- 230000001976 improved effect Effects 0.000 abstract description 5
- 235000018102 proteins Nutrition 0.000 description 654
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 110
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 110
- 229940024606 amino acid Drugs 0.000 description 49
- 235000001014 amino acid Nutrition 0.000 description 49
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 37
- 241000589242 Legionella pneumophila Species 0.000 description 34
- 241000700159 Rattus Species 0.000 description 28
- 241000244201 Caenorhabditis briggsae Species 0.000 description 27
- 229940115932 legionella pneumophila Drugs 0.000 description 26
- 241000244203 Caenorhabditis elegans Species 0.000 description 24
- 208000006011 Stroke Diseases 0.000 description 21
- 241000607479 Yersinia pestis Species 0.000 description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 18
- 201000010099 disease Diseases 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 239000001301 oxygen Substances 0.000 description 18
- 229910052760 oxygen Inorganic materials 0.000 description 18
- 241000255313 Drosophila pseudoobscura Species 0.000 description 16
- 229940082615 organic nitrates used in cardiac disease Drugs 0.000 description 16
- 238000009472 formulation Methods 0.000 description 14
- 241000256844 Apis mellifera Species 0.000 description 13
- 210000002381 plasma Anatomy 0.000 description 13
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 12
- 241001670248 Saccharophagus degradans Species 0.000 description 12
- 241000422914 Tetraodon nigroviridis Species 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 241000607598 Vibrio Species 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 11
- 241000282898 Sus scrofa Species 0.000 description 10
- 230000001580 bacterial effect Effects 0.000 description 10
- 230000003647 oxidation Effects 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- 241000894007 species Species 0.000 description 10
- 241001490489 Oryzias curvinotus Species 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000010561 standard procedure Methods 0.000 description 9
- 241000282575 Gorilla Species 0.000 description 8
- 241000258124 Hemicentrotus pulcherrimus Species 0.000 description 8
- 102000008100 Human Serum Albumin Human genes 0.000 description 8
- 108091006905 Human Serum Albumin Proteins 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 241001272836 gamma proteobacterium HTCC2207 Species 0.000 description 8
- 210000002216 heart Anatomy 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 208000010125 myocardial infarction Diseases 0.000 description 8
- 238000002864 sequence alignment Methods 0.000 description 8
- 206010010774 Constipation Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- -1 Poly(ethylene glycol) Polymers 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 108020001507 fusion proteins Proteins 0.000 description 7
- 102000037865 fusion proteins Human genes 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 208000003243 intestinal obstruction Diseases 0.000 description 7
- 229910052742 iron Inorganic materials 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 230000024883 vasodilation Effects 0.000 description 7
- 102000009027 Albumins Human genes 0.000 description 6
- 108010088751 Albumins Proteins 0.000 description 6
- 241000192542 Anabaena Species 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 6
- 208000010228 Erectile Dysfunction Diseases 0.000 description 6
- 108010078321 Guanylate Cyclase Proteins 0.000 description 6
- 102000014469 Guanylate cyclase Human genes 0.000 description 6
- 241000342361 Magnetococcus Species 0.000 description 6
- 241000191043 Rhodobacter sphaeroides Species 0.000 description 6
- 206010047139 Vasoconstriction Diseases 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 201000001881 impotence Diseases 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 6
- 102000034285 signal transducing proteins Human genes 0.000 description 6
- 108091006024 signal transducing proteins Proteins 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000025033 vasoconstriction Effects 0.000 description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- 241000379619 Ruegeria Species 0.000 description 5
- 101150002402 Smcp gene Proteins 0.000 description 5
- 230000036983 biotransformation Effects 0.000 description 5
- 238000004364 calculation method Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 229940118696 vibrio cholerae Drugs 0.000 description 5
- 241000237370 Aplysia californica Species 0.000 description 4
- 241001041715 Caldicellulosiruptor saccharolyticus DSM 8903 Species 0.000 description 4
- 241000282465 Canis Species 0.000 description 4
- 241000282693 Cercopithecidae Species 0.000 description 4
- 241000195597 Chlamydomonas reinhardtii Species 0.000 description 4
- 241000193403 Clostridium Species 0.000 description 4
- 241000193449 Clostridium tetani Species 0.000 description 4
- 241001135745 Colwellia psychrerythraea Species 0.000 description 4
- 241000283073 Equus caballus Species 0.000 description 4
- 241000282324 Felis Species 0.000 description 4
- 241000025945 Flavobacteria bacterium BBFL7 Species 0.000 description 4
- 241000238820 Gryllus bimaculatus Species 0.000 description 4
- 241000045411 Hahella chejuensis Species 0.000 description 4
- 102000008015 Hemeproteins Human genes 0.000 description 4
- 108010089792 Hemeproteins Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 241000282619 Hylobates lar Species 0.000 description 4
- 241001139251 Jannaschia Species 0.000 description 4
- 241000288904 Lemur Species 0.000 description 4
- 241000282560 Macaca mulatta Species 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 241001486857 Oceanobacter Species 0.000 description 4
- 241000605012 Oceanospirillum Species 0.000 description 4
- 241000282577 Pan troglodytes Species 0.000 description 4
- 241000607568 Photobacterium Species 0.000 description 4
- 241001272553 Photobacterium angustum S14 Species 0.000 description 4
- 241000282405 Pongo abelii Species 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 241000695265 Pseudoalteromonas atlantica T6c Species 0.000 description 4
- FEWCTJHCXOHWNL-UHFFFAOYSA-N Roxatidine acetate hydrochloride Chemical compound Cl.CC(=O)OCC(=O)NCCCOC1=CC=CC(CN2CCCCC2)=C1 FEWCTJHCXOHWNL-UHFFFAOYSA-N 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 239000003633 blood substitute Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 230000002779 inactivation Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229940124549 vasodilator Drugs 0.000 description 4
- 239000003071 vasodilator agent Substances 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 241000769734 Acidiphilium cryptum JF-5 Species 0.000 description 3
- 241000607620 Aliivibrio fischeri Species 0.000 description 3
- 241001149240 Alkaliphilus metalliredigens QYMF Species 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 101100282613 Drosophila melanogaster Gyc89Da gene Proteins 0.000 description 3
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 3
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 3
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 3
- 241001329728 Paracoccus denitrificans PD1222 Species 0.000 description 3
- 241001256940 Psychroflexus torquis ATCC 700755 Species 0.000 description 3
- 241000030574 Ruegeria pomeroyi Species 0.000 description 3
- 241001272841 Vibrio alginolyticus 12G01 Species 0.000 description 3
- 241000607272 Vibrio parahaemolyticus Species 0.000 description 3
- 241000607265 Vibrio vulnificus Species 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 210000002249 digestive system Anatomy 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 108010019130 nitrophorin Proteins 0.000 description 3
- 238000012014 optical coherence tomography Methods 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 230000006320 pegylation Effects 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000012460 protein solution Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- SEKGMJVHSBBHRD-WZHZPDAFSA-M vibal Chemical compound N#C[Co]N([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O SEKGMJVHSBBHRD-WZHZPDAFSA-M 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 102000006410 Apoproteins Human genes 0.000 description 2
- 108010083590 Apoproteins Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 101000977023 Azospirillum brasilense Uncharacterized 17.8 kDa protein in nodG 5'region Proteins 0.000 description 2
- 101000961984 Bacillus thuringiensis Uncharacterized 30.3 kDa protein Proteins 0.000 description 2
- 101100448223 Caenorhabditis elegans gcy-1 gene Proteins 0.000 description 2
- 241000195585 Chlamydomonas Species 0.000 description 2
- 101000644901 Drosophila melanogaster Putative 115 kDa protein in type-1 retrotransposable element R1DM Proteins 0.000 description 2
- 101000747702 Enterobacteria phage N4 Uncharacterized protein Gp2 Proteins 0.000 description 2
- 101000758599 Escherichia coli Uncharacterized 14.7 kDa protein Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241001430395 Halothermothrix orenii Species 0.000 description 2
- 241000139946 Halothermothrix orenii H 168 Species 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- 101000768930 Lactococcus lactis subsp. cremoris Uncharacterized protein in pepC 5'region Proteins 0.000 description 2
- 101000976302 Leptospira interrogans Uncharacterized protein in sph 3'region Proteins 0.000 description 2
- 101000778886 Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601) Uncharacterized protein LA_2151 Proteins 0.000 description 2
- 241000256010 Manduca Species 0.000 description 2
- 101710085938 Matrix protein Proteins 0.000 description 2
- 101710127721 Membrane protein Proteins 0.000 description 2
- 108010062374 Myoglobin Proteins 0.000 description 2
- 102100030856 Myoglobin Human genes 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 241000192656 Nostoc Species 0.000 description 2
- 108010064719 Oxyhemoglobins Proteins 0.000 description 2
- 101001121571 Rice tungro bacilliform virus (isolate Philippines) Protein P2 Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 101000818098 Spirochaeta aurantia Uncharacterized protein in trpE 3'region Proteins 0.000 description 2
- 101001026590 Streptomyces cinnamonensis Putative polyketide beta-ketoacyl synthase 2 Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 2
- 101000750896 Synechococcus elongatus (strain PCC 7942 / FACHB-805) Uncharacterized protein Synpcc7942_2318 Proteins 0.000 description 2
- 101000916321 Xenopus laevis Transposon TX1 uncharacterized 149 kDa protein Proteins 0.000 description 2
- 101000760088 Zymomonas mobilis subsp. mobilis (strain ATCC 10988 / DSM 424 / LMG 404 / NCIMB 8938 / NRRL B-806 / ZM1) 20.9 kDa protein Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 102000028546 heme binding Human genes 0.000 description 2
- 108091022907 heme binding Proteins 0.000 description 2
- 108010036302 hemoglobin AS Proteins 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 150000002823 nitrates Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 102220194781 rs199780731 Human genes 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 230000037432 silent mutation Effects 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- FOSISNXVGQBIAP-ALCCZGGFSA-N (Z)-diethylamino-hydroxyimino-oxidoazanium Chemical compound CCN(CC)[N+](\[O-])=N\O FOSISNXVGQBIAP-ALCCZGGFSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 241000588849 Acidiphilium cryptum Species 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 101100121606 Caenorhabditis elegans gcy-3 gene Proteins 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241001110912 Clostridium beijerinckii NCIMB 8052 Species 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 241000605716 Desulfovibrio Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000010750 Metalloproteins Human genes 0.000 description 1
- 108010063312 Metalloproteins Proteins 0.000 description 1
- 108010061951 Methemoglobin Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 241000186366 Mycobacterium bovis Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 229910004878 Na2S2O4 Inorganic materials 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 241001057811 Paracoccus <mealybug> Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000258128 Strongylocentrotus purpuratus Species 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- 108050009020 Truncated hemoglobin Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000607594 Vibrio alginolyticus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 210000001736 capillary Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000002146 exchange transfusion Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000003473 flash photolysis reaction Methods 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000000569 greater omentum Anatomy 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 230000001965 increasing effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 108010042248 nitrosyl hemoglobin Proteins 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- CMFNMSMUKZHDEY-UHFFFAOYSA-N peroxynitrous acid Chemical compound OON=O CMFNMSMUKZHDEY-UHFFFAOYSA-N 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43536—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms
- C07K14/4354—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms from nematodes
- C07K14/43545—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms from nematodes from Caenorhabditis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43563—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43563—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects
- C07K14/43577—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects from flies
- C07K14/43581—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects from flies from Drosophila
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/102499—Blood gas standard or control
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Cardiology (AREA)
- Insects & Arthropods (AREA)
- Tropical Medicine & Parasitology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
L'invention concerne des protéines H-NOX qui sont mutées pour obtenir des propriétés de cinétique et de thermodynamique de libération de NO gazeux dans le sang améliorées ou optimales. Les protéines H-NOX modifiées comprennent des mutations qui entraînent une modification de la liaison de NO ou de O2 avec le ligand, par rapport au domaine H-NOX de type sauvage correspondant, et peuvent être employés en tant que vecteurs sanguins de NO gazeux physiologiquement compatibles chez les mammifères. La présente invention concerne également des compositions pharmaceutiques, des kits et des méthodes utilisant les protéines H-NOX sauvages ou mutantes dans le traitement de tout état pathologique dans lequel la libération de NO est avantageuse.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US92150506P | 2006-05-22 | 2006-05-22 | |
US60/921,505 | 2006-05-22 | ||
PCT/US2007/012133 WO2007139767A2 (fr) | 2006-05-22 | 2007-05-21 | Préparations et méthodes pour la libération d'oxyde nitrique |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2653101A1 true CA2653101A1 (fr) | 2007-12-06 |
CA2653101C CA2653101C (fr) | 2016-12-13 |
Family
ID=38779160
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2653101A Active CA2653101C (fr) | 2006-05-22 | 2007-05-21 | Preparations et methodes pour la liberation d'oxyde nitrique |
CA2653080A Active CA2653080C (fr) | 2006-05-22 | 2007-05-21 | Compositions et procedes pour administrer de l'oxygene |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2653080A Active CA2653080C (fr) | 2006-05-22 | 2007-05-21 | Compositions et procedes pour administrer de l'oxygene |
Country Status (13)
Country | Link |
---|---|
US (7) | US8404632B2 (fr) |
EP (7) | EP2463297B1 (fr) |
JP (5) | JP5698905B2 (fr) |
CN (5) | CN108273040A (fr) |
AU (2) | AU2007268028B2 (fr) |
BR (2) | BRPI0711767B8 (fr) |
CA (2) | CA2653101C (fr) |
DK (4) | DK2463294T3 (fr) |
ES (4) | ES2611157T3 (fr) |
HK (1) | HK1129688A1 (fr) |
IN (2) | IN2013MN00601A (fr) |
NZ (4) | NZ594457A (fr) |
WO (2) | WO2007139791A2 (fr) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2463297B1 (fr) | 2006-05-22 | 2016-10-19 | The Regents of The University of California | Compositions et procédés de fourniture d'oxygène |
US20110243849A1 (en) * | 2010-04-02 | 2011-10-06 | Marletta Michael A | Heme-binding photoactive polypeptides and methods of use thereof |
US10385116B2 (en) | 2013-01-07 | 2019-08-20 | Omniox, Inc. | Polymeric forms of H-NOX proteins |
AU2016232866B2 (en) * | 2015-03-17 | 2021-10-21 | Omniox, Inc. | Modulation of tumor immunity by protein-mediated 02 delivery |
US20200276265A1 (en) * | 2016-02-16 | 2020-09-03 | Omniox, Inc. | Modulation hypoxia associated with stroke |
JP6467073B2 (ja) * | 2018-01-04 | 2019-02-06 | オムニオクス, インコーポレイテッド | H−noxタンパク質の重合体形態 |
EP3836911A1 (fr) | 2018-08-15 | 2021-06-23 | Omniox, Inc. | Protéines h-nox pour le traitement d'affections cardiovasculaires et pulmonaires |
EP3990476A1 (fr) | 2019-06-25 | 2022-05-04 | Gilead Sciences, Inc. | Protéines de fusion flt3l-fc et procédés d'utilisation |
US11795223B2 (en) | 2019-10-18 | 2023-10-24 | Forty Seven, Inc. | Combination therapies for treating myelodysplastic syndromes and acute myeloid leukemia |
AU2020374947A1 (en) | 2019-10-31 | 2022-03-31 | Forty Seven, Inc. | Anti-CD47 and anti-CD20 based treatment of blood cancer |
TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
MX2022007930A (es) | 2019-12-24 | 2022-08-08 | Carna Biosciences Inc | Compuestos moduladores de diacilglicerol quinasa. |
PE20231067A1 (es) | 2020-02-14 | 2023-07-17 | Jounce Therapeutics Inc | Anticuerpos y proteinas de fusion que se unen a ccr8 y usos de estos |
MX2022013619A (es) | 2020-05-01 | 2022-11-16 | Gilead Sciences Inc | Compuestos de 2,4-dioxopirimidina que inhiben cd73. |
TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | CD47/SIRPα結合及NEDD8活化酶E1調節次單元之共抑制以用於治療癌症 |
WO2022245671A1 (fr) | 2021-05-18 | 2022-11-24 | Gilead Sciences, Inc. | Méthodes d'utilisation de protéines de fusion flt3l-fc |
IL309378A (en) | 2021-06-23 | 2024-02-01 | Gilead Sciences Inc | DIACYLGLYERCOL KINASE MODULATING COMPOUNDS |
US11926628B2 (en) | 2021-06-23 | 2024-03-12 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
KR20240023628A (ko) | 2021-06-23 | 2024-02-22 | 길리애드 사이언시즈, 인코포레이티드 | 디아실글리세롤 키나제 조절 화합물 |
WO2022271684A1 (fr) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Composés modulant les diacylglycérol kinases |
CN118139858A (zh) | 2021-10-28 | 2024-06-04 | 吉利德科学公司 | 吡地嗪-3(2h)-酮衍生物 |
AU2022376954A1 (en) | 2021-10-29 | 2024-05-02 | Gilead Sciences, Inc. | Cd73 compounds |
AU2022419982A1 (en) | 2021-12-22 | 2024-06-06 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
WO2023122615A1 (fr) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Agents de dégradation des doigts de zinc de la famille ikaros et leurs utilisations |
TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
TW202346277A (zh) | 2022-03-17 | 2023-12-01 | 美商基利科學股份有限公司 | Ikaros鋅指家族降解劑及其用途 |
WO2023183817A1 (fr) | 2022-03-24 | 2023-09-28 | Gilead Sciences, Inc. | Polythérapie pour le traitement de cancers exprimant trop -2 |
TW202345901A (zh) | 2022-04-05 | 2023-12-01 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
US20230374036A1 (en) | 2022-04-21 | 2023-11-23 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
WO2024006929A1 (fr) | 2022-07-01 | 2024-01-04 | Gilead Sciences, Inc. | Composés cd73 |
WO2024064668A1 (fr) | 2022-09-21 | 2024-03-28 | Gilead Sciences, Inc. | POLYTHÉRAPIE ANTICANCÉREUSE PAR RAYONNEMENT IONISANT FOCAL ET PERTURBATION CD47/SIRPα |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4873192A (en) * | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
US6022849A (en) * | 1987-05-16 | 2000-02-08 | Baxter Biotech Technology Saarl | Mutant recombinant hemoglobins containing heme pocket mutations |
US5731454A (en) * | 1990-02-12 | 1998-03-24 | Virginia Commonwealth University | Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood |
WO1995027040A1 (fr) * | 1994-04-01 | 1995-10-12 | Unisyn Technologies, Inc. | Additifs pour un milieu de culture destine a des bioreacteurs a fibres creuses |
ATE302019T1 (de) * | 1997-02-28 | 2005-09-15 | Univ California | Verfahren und zusammensetzungen zur optimierung des sauerstofftransportes in zellfreien systemen |
DE69839263T2 (de) | 1997-05-02 | 2009-04-30 | Baxter Biotech Technology S.A.R.L. | Hämoglobin-Mutanten mit verringertem Stickstoff(mon)oxid-Entfernungsvermögen |
DE19837015C2 (de) * | 1998-08-14 | 2003-03-20 | Vasopharm Biotech Gmbh | Isolierte und gereinigte humane lösliche Guanylylcyclase alpha1/beta1 (hsGCalpha1/beta1) |
US6773613B1 (en) * | 1998-10-15 | 2004-08-10 | Sangart, Inc. | Method for production of stroma-free hemoglobin |
ES2383763T3 (es) * | 1999-12-22 | 2012-06-26 | The Scripps Research Institute | Composiciones farmacéuticas que comprenden Src y/o Yes y su utilización |
EP1294868A2 (fr) * | 2000-06-29 | 2003-03-26 | Incyte Genomics, Inc. | Adenylyl et guanylyl cyclases |
US20030096240A1 (en) * | 2000-09-19 | 2003-05-22 | Ferid Murad | Genomic organization of mouse and human sGC |
US6780849B2 (en) * | 2000-12-21 | 2004-08-24 | Scimed Life Systems, Inc. | Lipid-based nitric oxide donors |
US20030153491A1 (en) * | 2002-01-11 | 2003-08-14 | Winslow Robert M. | Methods and compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin |
DE60333306D1 (de) * | 2002-08-30 | 2010-08-19 | Biorexis Pharmaceutical Corp | Modifizierte transferrin-fusionsproteine mit doppelten transferrin-amino- oder carboxy-terminalen domänen |
CN1660100A (zh) * | 2002-12-09 | 2005-08-31 | 上海倍艺医药科技有限公司 | 一种治疗糖尿病及其并发症的药物 |
EP2463297B1 (fr) | 2006-05-22 | 2016-10-19 | The Regents of The University of California | Compositions et procédés de fourniture d'oxygène |
-
2007
- 2007-05-21 EP EP11189814.4A patent/EP2463297B1/fr active Active
- 2007-05-21 EP EP11189812A patent/EP2463296A1/fr not_active Withdrawn
- 2007-05-21 NZ NZ594457A patent/NZ594457A/xx unknown
- 2007-05-21 WO PCT/US2007/012184 patent/WO2007139791A2/fr active Application Filing
- 2007-05-21 AU AU2007268028A patent/AU2007268028B2/en active Active
- 2007-05-21 EP EP11189808A patent/EP2463295A1/fr not_active Withdrawn
- 2007-05-21 DK DK11189807.8T patent/DK2463294T3/en active
- 2007-05-21 US US12/302,004 patent/US8404632B2/en active Active
- 2007-05-21 WO PCT/US2007/012133 patent/WO2007139767A2/fr active Application Filing
- 2007-05-21 IN IN601MUN2013 patent/IN2013MN00601A/en unknown
- 2007-05-21 EP EP11189807.8A patent/EP2463294B1/fr active Active
- 2007-05-21 DK DK07795153.1T patent/DK2040740T3/en active
- 2007-05-21 CN CN201810357346.5A patent/CN108273040A/zh active Pending
- 2007-05-21 CA CA2653101A patent/CA2653101C/fr active Active
- 2007-05-21 JP JP2009512098A patent/JP5698905B2/ja active Active
- 2007-05-21 ES ES11189814.4T patent/ES2611157T3/es active Active
- 2007-05-21 IN IN600MUN2013 patent/IN2013MN00600A/en unknown
- 2007-05-21 ES ES07795153.1T patent/ES2525226T3/es active Active
- 2007-05-21 CN CN200780027797.2A patent/CN101495134B/zh active Active
- 2007-05-21 NZ NZ573004A patent/NZ573004A/en unknown
- 2007-05-21 EP EP07795153.1A patent/EP2040740B1/fr active Active
- 2007-05-21 US US12/302,002 patent/US8404631B2/en active Active
- 2007-05-21 EP EP07795174A patent/EP2032156B1/fr active Active
- 2007-05-21 BR BRPI0711767A patent/BRPI0711767B8/pt active IP Right Grant
- 2007-05-21 DK DK07795174.7T patent/DK2032156T3/da active
- 2007-05-21 NZ NZ594456A patent/NZ594456A/xx unknown
- 2007-05-21 CN CN201410766335.4A patent/CN104689300B/zh active Active
- 2007-05-21 BR BRPI0711901-1A patent/BRPI0711901A2/pt not_active Application Discontinuation
- 2007-05-21 CA CA2653080A patent/CA2653080C/fr active Active
- 2007-05-21 CN CN200780027798.7A patent/CN101495506B/zh active Active
- 2007-05-21 JP JP2009512107A patent/JP5698906B2/ja active Active
- 2007-05-21 ES ES07795174T patent/ES2399662T3/es active Active
- 2007-05-21 DK DK11189814.4T patent/DK2463297T3/en active
- 2007-05-21 AU AU2007268052A patent/AU2007268052B2/en active Active
- 2007-05-21 ES ES11189807.8T patent/ES2610653T3/es active Active
- 2007-05-21 NZ NZ573003A patent/NZ573003A/en unknown
- 2007-05-21 CN CN201610487363.1A patent/CN106075388B/zh active Active
- 2007-05-21 EP EP11189818A patent/EP2474554A3/fr not_active Withdrawn
-
2009
- 2009-09-07 HK HK09108182.2A patent/HK1129688A1/xx unknown
-
2013
- 2013-02-20 US US13/772,281 patent/US20130288970A1/en not_active Abandoned
- 2013-02-20 US US13/772,283 patent/US20130289252A1/en not_active Abandoned
-
2014
- 2014-09-04 JP JP2014180140A patent/JP6118772B2/ja active Active
- 2014-09-04 JP JP2014180132A patent/JP6118296B2/ja active Active
- 2014-09-17 US US14/489,395 patent/US9493526B2/en active Active
- 2014-09-18 US US14/490,597 patent/US9493527B2/en active Active
-
2016
- 2016-10-12 US US15/292,012 patent/US10202428B2/en active Active
-
2017
- 2017-03-27 JP JP2017061455A patent/JP6458070B2/ja active Active
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9493527B2 (en) | Compositions and methods for the delivery of nitric oxide | |
AU2013201114B2 (en) | Compositions and Methods for the Delivery of Nitric Oxide | |
AU2013201117B2 (en) | Compositions and Methods for the Delivery of Oxygen |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request |